Infection control methods for cancer patients undergoing treatment The base of evidence. by author

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1 ECCMID 2011, Milano Infection control methods for cancer patients undergoing treatment The base of evidence Mical Paul Rabin Medical Center; Beilinson Hospital Tel-Aviv University, Israel

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4 30-something years later

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9 Where are the limits?

10 ECIL guidelines Eur J Cancer 2007 IDSA guidelines Clin Infect Dis 2010 Antibiotic prophylaxis CDC/SHEA, BMT societies BMT 2009

11 Antifungal prophylaxis IDSA Prophylaxis against Candida allogeneic HSCT, intensive remission-induction or salvage-induction chemotherapy for acute leukemia (A-I) A mold-active anticipated prolonged neutropenic periods of at least 2 weeks (C-III), or a prolonged period of neutropenia immediately prior to HSCT (C-III) Posaconazole acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) in whom the risk of invasive aspergillosis without prophylaxis is substantial (B-I) Patients with prior invasive aspergillosis (A-III), ECIL Acute leukemia induction: posaconazole (A-I); fluconazole (C-I) Allogeneic HSCT preengraftment: fluconazole, voriconazole (A-I); itraconazole solution (B-I) Allogeneic HSCT + GVHD: posaconazole, voriconazole (A-I); itraconazole solution (B-I) Secondary prophylaxis: based on previous infection (A-II)

12 Non-pharmacological measures Infection control

13 Questions What is the empirical evidence available for infection control interventions? What are the effects of these interventions? What are the effects for patients at various risks for infection?

14 What are we asking? The clinical trials were designed to evaluate the entire PEPA (protective environment prophylactic antibiotics) program and not just air filtration... on the outcome of the chemotherapy complete remission rates, the duration of remission, and survival. The relevant outcome is all-cause mortality Bodey GP, Freireich EJ: Influence of high-efficiency particulate air filtration on mortality and fungal infection: a rebuttal. J Infect Dis 2006.

15 Review of evidence Studies considered Prospective comparative studies: randomized controlled trials, controlled clinical trials, prospectively planned or prospective data collection for comparative cohort studies, historically controlled trials, before-after studies and interrupted time series. Conducted in non-outbreak settings All cancer patients Update of: Schlesinger A, Paul M, Gafter-Gvili A, Rubinovitch B, Leibovici L. Infection-control interventions for cancer patients after chemotherapy: a systematic review and meta-analysis. Lancet Infect Dis Feb;9(2):97-107

16 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

17 Air filtration +/- various barrier isolation or endogenous suppression interventions 14 randomized controlled trials Description of studies 26 Protective isolation 12 quasi-rct and non-randomized Inpatient vs. outpatient 11 non-randomized prospective comparative studies 3 Neutropenic diet 3 Randomized Masks for transport Footwear exchange Shinki bioclean rooms 3 other 1 RCT 2 non-randomized

18 Cancer/ risk Included patients Trials (43) Acute leukemia 33 Other hematological 7 Breast cancer + HSCT 2 Sarcoma 1 Allogeneic BMT/ HSCT 15 Autotologous/ combined HSCT 11 Children included 16

19 Results protective isolation

20 All-cause mortality Including all studies reporting on mortality FU closest to 100 days RR 0.79 [ ]

21 30 day follow-up RR 0.60 [ ]

22 100 day follow-up RR 0.78 [ ]

23 Longest FU up to 3 years RR 0.86 [ ]

24 Secondary outcomes Outcome Any CDI/ MDI Bacteremia Gram-negative MDI N studies N patients RR 95% CI to to to 0.66 Gram-positive to 0.79 MDI

25 Secondary outcomes Outcome N studies N patients RR 95% CI Mold to 1.53 infections Candida sp. IFI Infectionrelated mortality to to 0.93

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27 Gafter-Gvili et al. Meta-Analysis: Antibiotic Prophylaxis Reduces Mortality in Neutropenic Patients. Ann Intern Med 2005

28 Gafter-Gvili et al. Meta-Analysis: Antibiotic Prophylaxis Reduces Mortality in Neutropenic Patients. Ann Intern Med 2005

29 Conclusions - I Protective isolation results in a 40% (28-50%) relative risk reduction in 30-day all-cause mortality control of air quality barrier isolation antibiotic with antifungal prophylaxis, Effect smaller but still relevant statistically significant at long-term follow-up The independent contributions of barrier isolation and air quality control is unclear

30 Results Outpatient therapy

31 Study description All 11 non-randomized HSCT patients Autologous 8 Allogeneic 4 Neutropenic fever could be managed at home Pooled mean difference in hospital stay 13 days (12-14)

32 All-cause mortality

33 Any infection (CDI/ MDI) Bacteremia

34 Conclusions - II Outpatient therapy in non-randomized studies was not associated with an increased risk of death and was associated with a significantly lower risk for infections Prospective comparative studies have paved the way for future randomized controlled trials assessing outpatient HSCT

35 Results Neutropenic diet

36 Intervention Gardner 2008 Moody 2006 van Tiel 2007 Neutropenic diet No raw fruits or vegetables FDA+ no raw fruits or vegetables, aged cheeses, cold meat cuts, fast food, and take-out food No raw vegetables, salads, soft cheeses, raw meat products, most fresh fruits, tap water and spices added after cooking. Individually packed/single serving containers. Control Encouraged to eat fresh fruits and vegetables FDA-endorsed food safety guidelines Normal hospital diet

37 Major infections

38 Bacteremia/ fungemia

39 Conclusions - III Existing evidence supports low bacterial diet in the prevention of bacteremia Patients with acute leukemia With antibiotic prophylaxis Confidence intervals for any infection ( ) leave place for more trials assessing this intervention

40 Other interventions

41 Results Before-after design Staff and patients families exchange ordinary shoes for clean shoes to wear in the protected environment RCT Patients wear N95/ FFP2 masks when transported outside their rooms in the Hospital. No prophylaxis against Aspergillus sp

42 Summary

43 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

44 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

45 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

46 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

47 Interventions Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

48 Conclusion Mechanism Inhalation Endogenous source Normal flora Acquired Intervention Control of air quality: HEPA filtration, directed air flow (e.g. laminar airflow), positive pressure, air exchange, room sealing, upholstery, carpets, flowers, plants, patient masks for transport Endogenous flora suppression: Patient skin disinfection, oral hygiene, decontamination (topical, non-absorbable, systemic), low-bacterial diet Barrier isolation: gloves, gowns, shoe covers/ exchange, masks, hand hygiene, single rooms, restriction of ill visitors, outpatient therapy

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50 Thank you